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Cryo-EM structure of a human spliceosome activated for step 2 of splicing

Author

Listed:
  • Karl Bertram

    (MPI for Biophysical Chemistry)

  • Dmitry E. Agafonov

    (MPI for Biophysical Chemistry)

  • Wen-Ti Liu

    (MPI for Biophysical Chemistry)

  • Olexandr Dybkov

    (MPI for Biophysical Chemistry)

  • Cindy L. Will

    (MPI for Biophysical Chemistry)

  • Klaus Hartmuth

    (MPI for Biophysical Chemistry)

  • Henning Urlaub

    (Bioanalytical Mass Spectrometry, MPI for Biophysical Chemistry
    Bioanalytics Group, Institute for Clinical Chemistry, University Medical Centre Göttingen)

  • Berthold Kastner

    (MPI for Biophysical Chemistry)

  • Holger Stark

    (MPI for Biophysical Chemistry)

  • Reinhard Lührmann

    (MPI for Biophysical Chemistry)

Abstract

Spliceosome rearrangements facilitated by RNA helicase PRP16 before catalytic step two of splicing are poorly understood. Here we report a 3D cryo-electron microscopy structure of the human spliceosomal C complex stalled directly after PRP16 action (C*). The architecture of the catalytic U2–U6 ribonucleoprotein (RNP) core of the human C* spliceosome is very similar to that of the yeast pre-Prp16 C complex. However, in C* the branched intron region is separated from the catalytic centre by approximately 20 Å, and its position close to the U6 small nuclear RNA ACAGA box is stabilized by interactions with the PRP8 RNase H-like and PRP17 WD40 domains. RNA helicase PRP22 is located about 100 Å from the catalytic centre, suggesting that it destabilizes the spliced mRNA after step two from a distance. Comparison of the structure of the yeast C and human C* complexes reveals numerous RNP rearrangements that are likely to be facilitated by PRP16, including a large-scale movement of the U2 small nuclear RNP.

Suggested Citation

  • Karl Bertram & Dmitry E. Agafonov & Wen-Ti Liu & Olexandr Dybkov & Cindy L. Will & Klaus Hartmuth & Henning Urlaub & Berthold Kastner & Holger Stark & Reinhard Lührmann, 2017. "Cryo-EM structure of a human spliceosome activated for step 2 of splicing," Nature, Nature, vol. 542(7641), pages 318-323, February.
    • Handle: RePEc:nat:nature:v:542:y:2017:i:7641:d:10.1038_nature21079
    DOI: 10.1038/nature21079
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    Cited by:

    1. Alexandra Bergfort & Marco Preußner & Benno Kuropka & İbrahim Avşar Ilik & Tarek Hilal & Gert Weber & Christian Freund & Tuğçe Aktaş & Florian Heyd & Markus C. Wahl, 2022. "A multi-factor trafficking site on the spliceosome remodeling enzyme BRR2 recruits C9ORF78 to regulate alternative splicing," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    2. Josef Pánek & Adriana Roithová & Nenad Radivojević & Michal Sýkora & Archana Bairavasundaram Prusty & Nicholas Huston & Han Wan & Anna Marie Pyle & Utz Fischer & David Staněk, 2023. "The SMN complex drives structural changes in human snRNAs to enable snRNP assembly," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

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